David H. Koch Institute for Integrative Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Nat Rev Mol Cell Biol. 2013 Sep;14(9):563-80. doi: 10.1038/nrm3640.
Coordinated progression through the cell cycle is a complex challenge for eukaryotic cells. Following genotoxic stress, diverse molecular signals must be integrated to establish checkpoints specific for each cell cycle stage, allowing time for various types of DNA repair. Phospho-Ser/Thr-binding domains have emerged as crucial regulators of cell cycle progression and DNA damage signalling. Such domains include 14-3-3 proteins, WW domains, Polo-box domains (in PLK1), WD40 repeats (including those in the E3 ligase SCF(βTrCP)), BRCT domains (including those in BRCA1) and FHA domains (such as in CHK2 and MDC1). Progress has been made in our understanding of the motif (or motifs) that these phospho-Ser/Thr-binding domains connect with on their targets and how these interactions influence the cell cycle and DNA damage response.
细胞周期的协调进展是真核细胞面临的一项复杂挑战。在受到遗传毒性应激后，必须整合多种分子信号来建立针对每个细胞周期阶段的检查点，从而为各种类型的 DNA 修复留出时间。磷酸丝氨酸/苏氨酸结合结构域已成为细胞周期进展和 DNA 损伤信号转导的关键调节剂。这类结构域包括 14-3-3 蛋白、WW 结构域、Polo 框结构域（在 PLK1 中）、WD40 重复序列（包括 E3 连接酶 SCF(βTrCP)中的那些）、BRCT 结构域（包括 BRCA1 中的那些）和 FHA 结构域（如 CHK2 和 MDC1 中）。我们在理解这些磷酸丝氨酸/苏氨酸结合结构域与其靶蛋白连接的基序（或基序）以及这些相互作用如何影响细胞周期和 DNA 损伤反应方面已经取得了进展。
